RESUMEN

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists change the gastric pH and reduce the intestinal absorption of nonheme iron. Case reports and case-control studies have demonstrated that absorption of iron is affected by gastric acidity, but the clinical importance of these drug-drug interactions has remained uncertain. OBJECTIVES: The present case-control study employed 2 million longitudinal claims in 2011-2018 in the Taiwan National Health Insurance Research Database to investigate the impact of PPIs/H2 antagonists on the occurrence of iron-deficiency anaemia (IDA). METHODS: The present study retrospectively compared exposure to PPIs/H2 antagonists for 1 year among 5,326 cases with IDA and 21,304 matched controls. The postdiagnosis prescribing pattern was also calculated to understand current practice. RESULTS: Long-term (≥2 month) use of PPIs/H2 antagonists resulted in a higher risk of developing IDA than noncontinuous use/nonuse of those drugs (adjusted odds ratio [aOR] = 2.36, 95% confidence interval [CI] = 1.94-2.86, P < 0.001). There were significant changes in the postdiagnosis prescribing patterns of PPIs/H2 antagonists. The risk of developing IDA remained significant in the female subgroup (aOR = 2.16, 95% CI = 1.73-2.70, P < 0.001) and was even more prominent in those aged ≥ 50 years (aOR = 2.68, 95% CI = 1.94-3.70, P < 0.05). CONCLUSIONS: This study found that long-term use of PPIs/H2 antagonists increased the risk of developing IDA, and there was strong evidence of prescription pattern adjustments postdiagnosis. Physicians and pharmacists should be aware of this risk when patients are expected to take or have been taking PPIs/H2 antagonists for the long term.

Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists, 2 kinds of gastric suppressants commonly used for gastroesophageal reflux disease, decrease iron absorption in the gut and thus increase the risk of developing iron-deficiency anaemia (IDA). We constructed a retrospective matched case-control study within the Taiwan National Health Insurance Research Database. The longer period of PPIs/H2 antagonists used, the higher risk of IDA was, with the highest risk in female elderly groups (adjusted odds ratio = 2.68 in females aged ≥ 50). PPI users had a higher risk than H2 antagonist users during the 1-year follow-up. The prescription patterns postdiagnosis of IDA witnessed considerable drops for both groups, with less than a 10th of original users remaining the usages (1.72% and 9.85% taking PPIs and H2 antagonists within 90 days after receiving a diagnosis, respectively). Physicians and pharmacists should be aware of the risk of developing IDA in patients currently undergoing or expected to take long-term gastric acid suppressants.

RESUMEN

Paclitaxel is a commonly used chemotherapeutic agent. To minimize the risk of hypersensitivity reactions (HSRs), which occur in approximately 16-42% of patients, premedication with dexamethasone, clemastine, and ranitidine was standard of care. As of October 2019, ranitidine is no longer available. We compared the risk of HSRs to paclitaxel with and without premedication with ranitidine, hypothesizing that the incidence of HSRs to paclitaxel will be similar. In this retrospective cohort study, all first-time paclitaxel users in the Groene Hart Hospital were included from January 2019 to August 2020. The primary outcome was the incidence of HSRs, using a Student's t-test. One-hundred and eight patients who were first-time users of paclitaxel in the Groene Hart Hospital met the inclusion criteria. Most patients were treated for breast or ovarian cancer, followed by lung cancer. Analysis of all 836 paclitaxel administrations was performed. Following 349 administrations with ranitidine as premedication, eight HSRs occurred (2.3%), while following 487 administrations without ranitidine, 12 HSRs occurred (2.5%), p-value of 0.87. An additional analysis on the occurrence of HSRs per patient was performed: 45 patients received premedication in the form of ranitidine, of which eight patients (17.8%) had a HSR. Sixty-three patients did not receive premedication in the form of ranitidine, of whom 10 (15.8%) had a HSR, p-value of .80. In conclusion, we found no difference in the incidence of HSRs during paclitaxel infusions between patients who received ranitidine as premedication versus those who did not.

Asunto(s)

RESUMEN

BACKGROUND: Proton pump inhibitors (PPIs) have been speculated to cause gastric wall uptake (GWU) in MPI scans. However, the uptake mechanism and prevention methods are less studied. In this prospective trial we aimed to evaluate the impact of gastroprotective medications on GWU and its solutions. METHODS: 351 consecutive patients, scheduled for 2-day rest/stress 99mTc-MIBI scan, were distributed into 5 groups. 3-7 days following the baseline rest scan, the stress scan was acquired after intervention in the trial group, consisting of patients with history of PPI intake, randomly assigned to 3 subgroups: discontinuing PPIs(A), replacement with H2 blockers (B), and continuing PPIs (C). Patients receiving H2 blockers, continued it as before (D) and the remaining patients were the control group (E). GWU was graded compared to the myocardial uptake. RESULTS: In the rest phase, all groups had significantly higher GWU compared to the control group. In the stress phase, group A had less GWU than group B (P-value < 0.05) and both of them had significantly less GWU compared to group C (P-value < 0.001). There was no significant difference between PPI discontinuation periods of 3-5 days versus 5-7 days. There was a significant association between duration of oral PPI intake, but not IV PPIs, and GWU. GWU was significantly lower with oral compared to IV PPI administration. CONCLUSION: PPIs significantly increase GWU and discontinuing them for at least 3-5 days significantly reduces GWU. H2 antagonists are a good alternative in patients who cannot tolerate dyspepsia symptoms.

Asunto(s)

RESUMEN

Background The increasing use of antithrombotic therapies in older patients has led to an increased risk of gastrointestinal (GI) bleeding in chronic nonsteroidal anti-inflammatory drug (NSAID) users. Therefore, there is a pressing need for GI prophylaxis in these high-risk patients. Objective To analyze prescribing patterns and factors associated with the use of gastroprotective agents (GPAs) among high-risk, chronic NSAID users. Setting National claims database including 20% of the total Korean population aged ≥ 65 years. Method In this cross-sectional study, we identified older adults prescribed traditional NSAIDs for > 90 days and classified them into high- and ultra-high-risk groups if they had one or two or more GI risk factors, respectively. Proton pump inhibitors or misoprostol prescribed for more than 80% of traditional NSAID treatment days was regarded as appropriate GI prophylaxis. Main outcome measure Prevalence and associated factors with appropriate GI prophylaxis. Results Among 69,992 chronic traditional NSAID users, 38.8% and 9.4% belonged to the high and ultra-high-risk groups; 13.2% and 19.9% received appropriate GI prophylaxis, respectively. The most frequently used GPA was histamine H2 antagonists. Multiple NSAID use, concomitant antiplatelets and anticoagulants, and prior GI ulcer history increased the likelihood of receiving appropriate GI prophylaxis. Advanced age (≥ 85 years), indications other than arthritis, and neurology specialists negatively affected appropriate GI prophylaxis use. Conclusion Approximately one in five chronic NSAID users, considered ultra-high risk, are prescribed appropriate GI prophylaxis in Korea. Advanced age, indications, and specialties of the prescriber all need to be considered when selecting target populations for interventions.

Asunto(s)

RESUMEN

Eosinophilic esophagitis (EoE) is an esophageal allergic inflammatory disorder often presenting with infant/toddler gastroesophageal reflux symptoms refractory to treatment, including acid suppression trials with histamine H2 antagonists and proton pump inhibitors. We propose to evaluate the impact of infant acid suppressant exposure in EoE. Geisinger's pediatric EoE cases were matched to controls (1:5 EoE case control ratio) using age, race, sex, and ages at other diagnoses of asthma, eczema, and environmental allergies, totaling 526 EoE cases and 2,630 controls. Comparisons between EoE cases and matched controls were tested with regard to rates of acid suppression use with H2 antagonists and PPIs during infancy. Our analyses found the use of acid suppression in infancy was positively associated with EoE: PPI (5.7% EoE cases vs. 1.6% controls; P < 0.0001), H2 antagonists (8.8% EoE cases vs. 4.5% controls; P < 0.0001). Additionally, analysis of EoE cases using acid suppression during infancy indicated a likelihood for the diagnosis with EoE at an earlier age. Early acid suppression use in infants is significantly associated with the diagnosis of EoE in childhood in this well-matched retrospective cohort study. The potential link warrants additional investigation. Our study further reinforces the evidence-based stewardship of acid suppressant use, especially in our most vulnerable populations.

Asunto(s)

RESUMEN

BACKGROUND: Melasma is a skin pigmentation disorder that remains resistant to available therapies. The exact cause of melasma is unknown. Histamine is an inflammatory factor. Its involvement in pigmentation is obscure. The aim of this study is to introduce an herbal antihistamine H2 receptor which is effective in these disorders. METHODS: This is a review study by searching the electronic databases and also Persian Medicine books, from 2000 to 2018 by the keywords such as H2 antagonist, H2 blocker and melasma. RESULTS: According to the researched studies, histamine can induce melanogenesis and melasma after a series of stages in the body. Also, Histamine, through receptors 2, triggers melasma. Therefore, it can be said that antihistamine H2 receptor can be effective in melasma. Considering chemical antihistamine, H2 receptors have side effects, such as digestive problems, H2 antagonists can be used in the treatment of diseases such as dyspepsia but they have multiple complications. On the other hand, there is an herbal H2 antagonist that can be useful for melasma due to having some special properties. CONCLUSION: Herbal H2 blockers should be noted in melasma treatment along with the topical drugs.

Asunto(s)

RESUMEN

PURPOSE: Hypomagnesemia is a common side effect of panitumumab. The effect of magnesium-containing supplement as a laxative and concomitant antacid (proton pump inhibitor and histamine H2 antagonist) administration on panitumumab-induced hypomagnesemia was retrospectively investigated. METHODS: Patients with advanced or recurrent colorectal cancer who received panitumumab were included in this study. Serum magnesium levels were extracted from the electronic medical records of 1753 administrations in 221 patients who received panitumumab. Serum magnesium levels in patients with or without oral magnesium-containing supplement and antacid treatment were compared using analysis of covariance as the number of panitumumab administration up to 16 times for covariates. RESULTS: The mean serum magnesium levels were significantly decreased with increasing number of panitumumab administrations (2.13 mg/dL at 1st vs. 1.55 mg/dL at 16th, p < 0.001). The use of oral magnesium-containing supplement significantly inhibited the decline in mean serum magnesium level (1.98 mg/dL vs. 1.78 mg/dL, p < 0.001). However, antacid use in patients receiving oral magnesium-containing supplement significantly decreased the effectiveness of the magnesium supplement on serum magnesium level (2.02 mg/dL vs. 1.93 mg/dL, p < 0.05). CONCLUSION: The use of oral magnesium-containing supplement might function as magnesium supplement based on the finding that use of oral magnesium-containing supplement during panitumumab administration decreased hypomagnesemia. However, combination of antacid decreased the supplemental effect of oral magnesium on hypomagnesemia. These results suggest the possibility that use of antacids during anti-EGFR antibody administration may promote hypomagnesemia.

Asunto(s)

RESUMEN

AIM: To quantify (i) indicated versus non-indicated prescribing of acid-suppression therapies (AST) in a tertiary paediatric hospital; (ii) patient, provider and hospital factors associated with non-indicated prescribing; and (iii) medication costs. METHODS: This was a prospective, electronic medical audit conducted at The Royal Children's Hospital (RCH) Melbourne in August-September 2016. Proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2 RA) prescriptions were extracted, with relevant patient, provider and hospital data. Logistic regression analysis of variables associated with indicated and non-indicated prescribing was undertaken. Costs of indicated and non-indicated prescriptions were estimated, with annual costs projected. RESULTS: There was more non-indicated than indicated prescribing across inpatient, outpatient and emergency department settings. Of the total 303 prescriptions analysed, 238 (78.5%) were non-indicated. Gastrostomy presence (odds ratio (OR) 5.51 (1.96-15.46), P = 0.001), consultant providers (OR 2.69 (1.23-5.87), P = 0.01) and inpatient setting (OR 2.35 (1.16-4.77), P = 0.02) were all associated with a higher likelihood of non-indicated prescribing. The child having a predisposing diagnosis was significantly associated with indicated prescribing (OR 0.41 (0.21-0.80), P = 0.009). A total of 75% of hospital and patient spending was for non-indicated prescriptions. Annual costs of non-indicated AST for Melbourne's RCH were projected to be $15 493. CONCLUSIONS: Non-indicated acid-suppression prescribing is common in a tertiary paediatric hospital and associated with gastrostomy presence, consultant providers and inpatient status. Future research should use qualitative methods to understand clinician and patient drivers of prescribing and use this information to develop and test targeted solutions to reduce non-indicated AST prescribing.

Asunto(s)

RESUMEN

BACKGROUND: Erlotinib is a drug used for the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer. Severe hepatotoxicity was observed in 4% to 31% of patients receiving erlotinib treatment prompting delay or termination of treatment. Only a few factors related to hepatotoxicity of erlotinib have been reported. No study has investigated the role of concomitant medications and erlotinib-induced hepatotoxicity. The aim of this study was to investigate the association between erlotinib-induced hepatotoxicity and various factors including concomitant medications in patients with NSCLC and pancreatic cancer. METHODS: From January 2014 to June 2017, a retrospective study was conducted in patients with NSCLC and pancreatic cancer, who were treated with erlotinib. Various data were reviewed, including sex, age, body weight, height, body surface area (BSA), underlying disease, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), smoking history, erlotinib dose, EGFR mutation, and concomitant drugs. RESULTS: The incidence of grade 2 or higher hepatotoxicity in the study group of patients was 17.2%. Multivariate analysis showed a 2.7-fold increase in hepatotoxicity with the concomitant use of CYP3A4 inducers. In NSCLC patients, co-administration of H2-antagonist/PPI increased hepatotoxicity 3.5-fold. Among the demographic factors, liver metastasis and age ≥ 65 years were significant risk factors in all study patients and NSCLC patients, respectively; the attributable risks for liver metastasis and age were 46.3% and 71.8%, respectively. Subgroup analysis using pancreatic cancer patients yielded marginally significant results with CYP3A4 inducers and erlotinib-induced hepatotoxicity. Liver metastasis and CYP3A4 inducers also shortened time to hepatotoxicity 2.1 and 2.3-fold, respectively. CONCLUSIONS: Our study showed that concomitant use of CYP3A4 inducers and H2-antagonist/PPI, liver metastasis, and age ≥ 65 were associated with erlotinib-induced hepatotoxicity. Thus, close monitoring of liver function is recommended, especially in patients using CYP3A4 inducers and anti-acid secreting agents.

Asunto(s)

RESUMEN

Crizotinib is an orally available tyrosine kinase inhibitor for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC). Despite that crizotinib-induced hepatotoxicity may cause a dose reduction or interruption that can affect the patient's treatment, there is no study to investigate factors for crizotinib-induced hepatotoxicity. The purpose of this study was to evaluate factors affecting crizotinib-induced hepatotoxicity. From February 2012 to April 2018, a retrospective study was performed on NSCLC patients treated with crizotinib. Various factors were reviewed including sex, age, body weight, height, body surface area, underlying disease, smoking history, genetic mutation, and concomitant drugs. Among 153 patients, incidence of crizotinib-induced hepatotoxicity of grade I or higher was 83% (n = 127). The presence of liver disease or HBV revealed significant effect on hepatotoxicity within 28 days after crizotinib administration in univariate analysis. Patients with liver disease or HBV carriers revealed 2.3 times the hazard of time to hepatotoxicity compared to those without liver disease or HBV. Use of H2-antagonist or H2-antagonist/proton pump inhibitor revealed 1.7 times the hazard of time to hepatotoxicity compared to those that did not use those medications. Thus, close monitoring of liver function is recommended, especially in patients with liver impairment or using anti-acid secreting agents.

Asunto(s)

RESUMEN

Gefitinib is a drug used for the treatment of non-small cell lung cancer (NSCLC) patients. Severe hepatotoxicity was observed, but only a few cases have been reported on the hepatotoxicity of gefitinib. This study aimed to investigate the association between gefitinib-induced hepatotoxicity and various factors including concomitant medications in lung cancer patients. From January 2013 to December 2014, a retrospective study was performed with NSCLC patients who were treated with gefitinib. Associations between hepatotoxicity and various factors including concomitant drugs were analyzed. Based on multivariate models, it was found that H2 antagonists, proton pump inhibitors (PPIs), and H2 antagonists or PPIs increased hepatotoxicity by about 1.5- to 1.7-fold. Patients younger than 65 years showed 1.6 times higher hepatotoxicity than those older than 65 years. Patients with EGFR mutations had around 2-fold higher hepatotoxicity, and the percentage of incidence of hepatotoxicity because of exon 19 deletion was 32.7%. Our study showed that anti-acid-secreting agents in addition to age younger than 65 years and EGFR mutation were associated with gefitinib-induced hepatotoxicity. Thus, close monitoring of liver function is recommended, especially for patients using anti-acid-secreting agents.

Asunto(s)

RESUMEN

Histamine receptor 2 (H2) antagonists are widely used clinically for the control of gastrointestinal symptoms, but also impact immune function. They have been reported to reduce tumor growth in established colon and lung cancer models. Histamine has also been reported to modify populations of myeloid-derived suppressor cells (MDSCs). We have examined the impact of the widely used H2 antagonist ranitidine, on both myeloid cell populations and tumor development and spread, in three distinct models of breast cancer that highlight different stages of cancer progression. Oral ranitidine treatment significantly decreased the monocytic MDSC population in the spleen and bone marrow both alone and in the context of an orthotopic breast tumor model. H2 antagonists ranitidine and famotidine, but not H1 or H4 antagonists, significantly inhibited lung metastasis in the 4T1 model. In the E0771 model, ranitidine decreased primary tumor growth while omeprazole treatment had no impact on tumor development. Gemcitabine treatment prevented the tumor growth inhibition associated with ranitidine treatment. In keeping with ranitidine-induced changes in myeloid cell populations in non-tumor-bearing mice, ranitidine also delayed the onset of spontaneous tumor development, and decreased the number of tumors that developed in LKB1(-/-)/NIC mice. These results indicate that ranitidine alters monocyte populations associated with MDSC activity, and subsequently impacts breast tumor development and outcome. Ranitidine has potential as an adjuvant therapy or preventative agent in breast cancer and provides a novel and safe approach to the long-term reduction of tumor-associated immune suppression.

RESUMEN

ABSTRACT Background Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Results Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. Conclusion The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions.

RESUMO Contexto Anti-inflamatórios não esteroidais induzem lesões da mucosa gástrica devido às suas propriedades ácidas. Ranitidina, um antagonista dos receptores H2, revelou-se benéfico em pacientes com úlceras gástricas. Objetivo - O presente estudo foi realizado para avaliar o efeito da administração de ranitidina em gastropatia induzida por anti-inflamatórios não esteroidais (diclofenaco, nimesulida) e seu efeito sobre a histopatologia do estômago, dos rins e fígado. Métodos Diclofenaco, nimesulida e ranitidina foram administradas em doses de 2, 4 e 6 mg/kg, p.o. uma vez diariamente por 14 dias e seu efeito sobre o volume gástrico, acidez, significam o número de úlcera e o pH gástrico. Além disso, o exame histopatológico também foi realizado em seções do estômago, dos rins e fígado. Resultados Após a administração de diclofenaco ou nimesulida, todos os parâmetros gástricos foram significativamente alterados assim como a histopatologia do estômago, fígado e rim. No grupo controle, as seções renais mostraram glomérulos normais sem espessamento da membrana basal glomerular, enquanto em diclofenaco isolado, nimesulida isolado e grupos com ranitidina e nimesulida, foi observado espessamento da membrana basal glomerular. Estas alterações observou-se serem revertidas no grupo ranitidina com diclofenaco. As seções do fígado, o grupo controle mostrou placas e cordões de hepatócitos cuboidais anastomosados com núcleos bem demarcados e citoplasma abundante. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, leve dilatação dos sinusoides é vista acoplados com proeminência de veia central. Nos grupos diclofenaco e nimesulida sozinhos, túbulos proximais e distais contorcidos mostram necrose tubular focal leve. Nas secções gástricas, o grupo controle mostrou várias dobras formando vilosidades e a superfície do revestimento epitelial da mucosa. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, o duodeno mostrou dispersas células inflamatórias predominantemente compostas por linfócitos. Nos grupos diclofenaco e nimesulida sozinhos, as secções de áreas gástricas mostraram necrose parcial e inflamação crônica moderada respectivamente. Conclusão - O estudo, portanto, forneceu o fundamento terapêutico para administração simultânea de bloqueador de receptor H2 (ranitidina) com diclofenaco, sendo mais benéfica em comparação com ranitidina com nimesulida para minimizar a intolerância gástrica de diclofenaco no tratamento a longo prazo de condições inflamatórias.

Asunto(s)

RESUMEN

BACKGROUND: The Surviving Sepsis Campaign suggests that proton pump inhibitors (PPIs) be considered over histamine-2-receptor antagonists (H2RA) for stress ulcer prophylaxis (SUP), but there are no studies demonstrating superiority with PPIs in this population. OBJECTIVE: To determine if H2RAs are associated with an increased risk for gastrointestinal (GI) bleeding in patients with severe sepsis or septic shock. METHODS: This study queried the Multiparameter Intelligent Monitoring in Intensive Care II database to identify adult patients with severe sepsis or septic shock requiring mechanical ventilation for at least 48 hours. Patients were excluded if they had GI bleeding as a primary diagnosis, variceal bleeding, received both PPIs and H2RAs or no acid suppression. Demographic characteristics, medication use and potential confounders for GI bleeding were recorded. ICD-9 coding was used to identify GI bleeding listed as a secondary diagnosis. Multivariate analysis was performed to assess the role of H2RAs as an independent risk factor for GI bleeding. RESULTS: There were 686 patients evaluated. The incidence of GI bleeding was 9.5%. Patients who received H2RAs had a bleeding incidence of 2.3% versus 10% with PPIs (P = 0.111). On controlling for confounding variables, drug selection (H2RA or PPI) was not associated with an increased risk for bleeding. Acute or chronic liver disease was the only independent risk factor identified: odds ratio [OR] (95% CI) = 3.75 (2.19-6.44); P < 0.001. CONCLUSION: H2RAs are not associated with an increased risk for GI bleeding in patients with severe sepsis or septic shock who require mechanical ventilation. These data do not support the Surviving Sepsis Campaign recommendation of PPIs as the preferred agent in this population.

Asunto(s)

RESUMEN

The neural mechanisms underlying levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) may involve histamine (H2) receptors on striatopallidal pathways. We recently demonstrated that the clinically available oral histamine H2 receptor antagonist (H2 RA), famotidine, can reduce l-dopa-induced chorea in MPTP-lesioned macaques. We hypothesized that famotidine may be useful in the treatment of LID in PD patients. We performed a proof-of-concept, double-blind, randomized, multiple cross-over (4×) trial. Seven PD subjects with bothersome dyskinesia were randomized to oral famotidine 80, 120, and 160 mg/day and placebo. Each subject was randomized to receive each of the four treatment phases for 14 days followed by a 7-day wash-out period between each treatment phase. The primary outcome measure was change in the Unified Dyskinesia Rating Scale (UDysRS; part III) between placebo and famotidine. Secondary outcomes were UDysRS (parts I and II), Global Impression of Change, Lang-Fahn Activities of Daily Living Dyskinesia Scale, Unified Parkinson's Disease Rating part III, and adverse events (AEs). Outcomes were evaluated pre- and post-treatment per dose and analyzed using a mixed-effects linear model. There was no significant effect of famotidine treatment on any of the primary or secondary outcome measures compared to placebo (each dose and all doses combined). There were no significant AEs. Even though the sample size of the current study is limited, famotidine seems to be safe in patients with PD and LID, but showed no potential as an antidyskinetic agent.

RESUMEN

The relationship between gastric mucosal blood flow (GMBF) and acid secretion was studied in rats by using secretory stimulant (pantagastrin) and inhibitor (cimetidine) GMBF was measured by laser Doppler flowmetry (LDF) and gastric mucosal pH determined by microglass pH electrode. GMBF was increased and gastric mucosal pH decreased significantly after intravenous injection of 6?g/kg of pcntagaslrin, while GMBF was decreased and gaslric mucosal pH increased markedly after intravenous administration of 109 mg/kg caretidine. This indicates that pentagastrin can increase GMBF and acid secretion, and cimctidine can decrease GMBF ang acid secretion.GBMF is closely relatel to acid secretion in rats